The IMPaCT trial: Individualised Molecular Pancreatic Cancer Therapy. A pilot, randomized, open label Phase II trial assessing first line treatment with gemcitabine or personalized treatment based on tumour molecular signature in patients with metastatic pancreatic cancer.

Background: Less than 5% of patients with metastatic pancreatic cancer survive to 5 years and there have been no major improvements in outcomes over the last 20 years. The use of treatments targeted according to the molecular phenotype of individual tumours may result in improved response and survival compared to standard therapy. Methods: The IMPaCT trial is a multidisciplinary collaboration between the AGITG, NHMRC Clinical Trials Centre, Sydney Catalyst, and the Kinghorn Cancer Centre at Garvan Institute of Medical Research, which houses the Australian Pancreatic Cancer Genome Initiative (APGI). Patients who have available sequence data will be screened for actionable molecular phenotypes and randomized 1:1 to receive standard therapy (gemcitabine) or personalized treatment. Recruitment to the IMPaCT trial is based on the following defined molecular phenotypes: HER2/neu overexpression: personalized treatment with gemcitabine + trastuzumab; BRCA1, BRCA2, and PALB2 mutations: personalized treatment with 5-FU and mitomycin C; Kras wildtype: personalized treatment with gemcitabine + erlotinib. The study will be conducted in two parts: an initial 20 patient pilot trial across 4 Australian sites assessing feasibility, followed by an additional 70 patients to assess progression (90 patients in total). The pilot study is now open and active. Results: The novel trial design involves personalized treatment, where therapies are assigned based on a defined molecular phenotype, in a standard care setting. Stratifying randomization for individual molecular signatures will provide evidence, albeit in small numbers, for confirmation in a larger Phase III trial and broader clinical applicability. Additionally, the study offers the opportunity to explore a number of unique tertiary/correlative objectives, including the planned examination of circulating DNA as a surrogate of survival. Conclusion: The IMPaCT trial exemplifies a strong collaboration between basic scientists, clinicians and clinical trial investigators to illustrate the promises and challenges facing the development and successful testing of personalized therapeutic strategies. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A75. Citation Format: Lorraine Chantrill, Amber Johns, Adnan Nagrial, Venessa Chin, Angela Chou, Mark Pinese, Scott Mead, Val Gebski, Katrin Sjoquist, Chee Lee, Sonia Yip, Danielle Miller, Lucille Sebastian, Ray Asghari, Sandra Harvey, Nick Pavlakis, Sanjay Mukhedkar, Peter Grimison, David Miller, John Pearson, Nicola Waddell, Sean Grimmond, John Simes, Andrew Biankin. The IMPaCT trial: Individualised Molecular Pancreatic Cancer Therapy. A pilot, randomized, open label Phase II trial assessing first line treatment with gemcitabine or personalized treatment based on tumour molecular signature in patients with metastatic pancreatic cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A75.